5576015 ROLE OF APOLIPOPROTEIN-1 GENE (APOL-1) AS A GENETIC PREDICTOR OF RENAL DYSFUNCTION AMONG SICKLE CELL DISEASE EGYPTIAN PEDIATRIC PATIENTS
Authors: I.S.A. Shaheen, N.M.S. Salama, O.Y.H. Yehia, E.Y.H. Youssef, M.H.M. Hamdy
Journal: HemaSphere (2023)

Background: Sickle cell nephropathy (SCN) is linked with significant morbidity and mortality. SCN is first presented as glomerular hyperfiltration then it progresses to focal segmental glomerular sclerosis, and eventually, renal failure. SCN can be assessed by the presence of albuminuria, measuring estimated glomerular filtration rate (eGFR), abnormalities in kidney biopsy and/or imaging, and. SCN was linked to different gene polymorphisms such as the apolipoprotein-1 (APOL-1) gene two haplotypes; G1 (G1GM and G1G+ sub- haplotypes) and G2. Aim: Determination of the prevalence of APOL-1 among SCD Egyptian pediatric patients and its role as a genetic predictor of renal dysfunction in SCD pediatric patients. Methods: In this cross-sectional study, 69 patients with sickle cell anemia (SCA) and 28 patients with S/β thalassemia patients, and 3 sickle trait patients underwent full history taking, clinical examination, and laboratory tests including CBC, Hb electrophoresis, serum creatinine (and calculation of eGFR using “bedside Schwartz” formula), microalbuminuria, urine albumin/ creatinine ratio and genomic DNA analysis for detection of APOL-1 G1 SNPs S342G and I384M using PCR- RFLP analysis. Results: The prevalence of APOL-1 G1 variants among our patients was 44% (44 patients); 23% of them had G1GM sub-haplotype (10% of SCD patients) and 77% of them had G1G+ sub-haplotype (34% of SCD patients). Among the 17 cases of microalbuminuria, 9 cases (53%) had G1 variants. Hyperfiltration cases were 10 cases of which 7 cases (70%) had the G1 variants, 13 out of the 30 cases (43.3%) of mildly decreased eGFR had G1 variants and the two cases of mild to moderately decreased eGFR (100%) had G1 variant; the G1GM sub-haplotype. There was no significant association between the APOL-1 G1 variant in total and the chronic renal complications of SCD in the studied patients. There was no significant association between G1GM sub-haplotype and the earlier stages of chronic kidney disease as hyperfiltration and mildly decreased eGFR. A significant association was found between G1GM sub-haplotype and later stages of chronic kidney disease; as microalbuminuria (P=0.026) and mildly to moderately decreased eGFR (P=0.020). Conclusion: The prevalence of APOL-1 G1 variants in our study was 44% with a higher prevalence of G1G+ sub-haplotype (34%) than G1GM sub-haplotype (10%). There is a significant association between having G1GM sub-haplotype and chronic renal complications; as microalbuminuria and mildly to moderately decreased eGFR, thus, APOL-1 risk variant G1GM was associated with more severe stages of chronic kidney disease, indicating a more prominent association with SCN progression. Keywords: Sickle cell disease, nephropathy, albuminuria, estimated glomerular filtration rate, APOL-1, G1 variants. References 1. Cachat F, Combescure C, Cauderay M, Girardin E, Chehade H (2015): A systematic review of glomerular hyperfiltration assessment and definition in the medical literature. Clin J Am Soc Nephrol; 10(3):382-389. 2. Ashley-Koch AE, Akocha C, Garrett ME, Telen MJ, Soldano K, De Castro LM, Jonassaint JC, Orringer EP, Eckman JR (2011): MYH9 and APOL1 are both associated with sickle cell disease nephropathy. BR J Haematol; 155(3):386-94.